1. Field of the Invention
The present invention relates generally to small molecules for inhibition of function of and drug delivery to leukocytes, and more particularly to small molecules that specifically recognize or have an affinity for LFA-1.
2. Description of the Prior Art
The interaction of lymphocyte function-associated antigen (LFA)-1 with its ligands, intercellular adhesion molecules ICAM-1, ICAM-2 and ICAM-3, mediates several steps leading to an inflammatory response and has an established role in leukocyte cell adhesion and further exerts its influence on cell trafficking and cell-cell contact. Woska, et al., “A small-molecule antagonist of LFA-1 blocks a conformational change important for LFA-1 function, Journal of Leukocyte Biology,” 70: 329-334 (August 2001), and Kelly, et al., “Cutting Edge: A Small Molecule Antagonist of LFA-1-Mediated Cell Adhesion,” Journal of Immunology, 163: 5173-5177 (1999), the entire contents and disclosures of which are hereby incorporated by reference herein. Leukocyte extravasation, antigen presentation, and T-cell effector functions are all mediated in part by LFA-1. However, most therapeutics designed to block the binding of LFA-1 to ICAM-1 have been mAb based.
Thus, there is still a need for appropriate small molecules for inhibition of function of and drug delivery to leukocytes that specifically recognize or have an affinity for LFA-1.